| First Author | Mizokami A | Year | 2010 |
| Journal | J Neurochem | Volume | 114 |
| Issue | 1 | Pages | 302-10 |
| PubMed ID | 20412381 | Mgi Jnum | J:161821 |
| Mgi Id | MGI:4461377 | Doi | 10.1111/j.1471-4159.2010.06754.x |
| Citation | Mizokami A, et al. (2010) GABA(A) receptor subunit alteration-dependent diazepam insensitivity in the cerebellum of phospholipase C-related inactive protein knockout mice. J Neurochem 114(1):302-10 |
| abstractText | The GABA(A) receptor, a pentamer composed predominantly of alpha, beta, and gamma subunits, mediates fast inhibitory synaptic transmission. We have previously reported that phospholipase C-related inactive protein (PRIP) is a modulator of GABA(A) receptor trafficking and that knockout (KO) mice exhibit a diazepam-insensitive phenotype in the hippocampus. The alpha subunit affects diazepam sensitivity; alpha1, 2, 3, and 5 subunits assemble with any form of beta and the gamma2 subunits to produce diazepam-sensitive receptors, whereas alpha4 or alpha6/beta/gamma2 receptors are diazepam-insensitive. Here, we investigated how PRIP is implicated in the diazepam-insensitive phenotype using cerebellar granule cells in animals expressing predominantly the alpha6 subunit. The expression of alpha1/beta/gamma2 diazepam-sensitive receptors was decreased in the PRIP-1 and 2 double KO cerebellum without any change in the total number of benzodiazepine-binding sites as assessed by radioligand-binding assay. Since levels of the alpha6 subunit were increased, the alpha1/beta/gamma2 receptors might be replaced with alpha6 subunit-containing receptors. Then, we further performed autoradiographic and electrophysiologic analyses. These results suggest that the expression of alpha6/delta receptors was decreased in cerebellar granule neurons, while that of alpha6/gamma2 receptors was increased. PRIP-1 and 2 double KO mice exhibit a diazepam-insensitive phenotype because of a decrease in diazepam-sensitive (alpha1/gamma2) and increase in diazepam-insensitive (alpha6/gamma2) GABA(A) receptors in the cerebellar granule cells. |
